胆囊癌组织中miR-103a-3p、SIX4表达及与患者临床病理特征和预后的关系

Expression of miR-103a-3p and SIX4 in gallbladder carcinoma and their relationships with pathological parameters and prognosis

目的探讨胆囊癌组织中微小RNA-103a-3p(miR-103a-3p)、SIX同源盒蛋白4(SIX4)表达及与患者临床病理特征和预后的关系。方法选择80例胆囊癌患者,取手术切除癌组织和癌旁组织,采用qRT-PCR法检测癌组织和癌旁组织中miR-103a-3p、SIX4表达,分析不同临床病理特征胆囊癌组织中miR-103a-3p、SIX4表达差异,Kaplan-Meier法分析不同miR-103a-3p、SIX4表达患者的生存差异,Cox比例风险回归模型分析胆囊癌患者预后的影响因素。结果胆囊癌组织中miR-103a-3p表达低于癌旁组织(P<0.05),SIX4表达高于癌旁组织(P<0.05)。TNM分期Ⅲ期、低分化、肝脏浸润、胆总管浸润、淋巴结转移患者miR-103a-3p表达低于TNM分期Ⅰ、Ⅱ期、中高分化和无肝脏浸润、无胆总管浸润、无淋巴结转移患者(P均<0.05),SIX4表达高于TNM分期Ⅰ、Ⅱ期、中高分化和无肝脏浸润、无胆总管浸润、无淋巴结转移患者(P均<0.05)。胆囊癌患者miR-103a-3p表达与SIX4表达呈负相关(r=-0.532,P<0.05)。随访期间患者死亡59例,miR-103a-3p低表达、SIX4高表达胆囊癌患者3年总生存率低于miR-103a-3p高表达、SIX4低表达患者(Log-Rankχ2分别为6.761、5.853,P均<0.05)。肝脏浸润、淋巴结转移、SIX4高表达是胆囊癌患者预后的危险因素(P均<0.05),miR-103a-3p高表达是保护因素(P<0.05)。结论胆囊癌组织中miR-103a-3p表达上调,SIX4表达下调,且与胆囊癌恶性临床病理特征和生存率低下有关。

Objective To investigate the expression of miR-103a-3p and sine oculis homeobox homolog 4(SIX4)in gallbladder carcinoma tissues and their relationships with pathological parameters and prognosis.Methods Eighty patients with gallbladder cancer were selected.The tumor tissues and adjacent tissues were removed surgically.The expression levels of miR-103a-3p and SIX4 in the cancer and adjacent tissues were detected by real-time quantitative polymerase chain reaction(qRT-PCR).The expression differences of miR-103a-3p and SIX4 in gallbladder cancer tissues with different pathological parameters were analyzed.Kaplan-Meier method was used to analyze the survival difference of patients with different miR-103a-3p and SIX4 expression levels,and Cox proportional risk regression model was used to analyze the prognostic factors of patients with gallbladder carcinoma.Results The expression of miR-103a-3p in the gallbladder carcinoma tissues was lower than that in the paracancer tissues(P<0.05),and the expression of SIX4 was higher than that in the paracancer tissues(P<0.05).The expression of miR-103a-3p in patients with TNM stageⅢ,low differentiation,liver invasion,common bile duct invasion,and lymph node metastasis was lower than that in patients with TNM stageⅠ-Ⅱ,medium and high differentiation,and patients without liver invasion,common bile duct invasion,and lymph node metasta‑sis(P<0.05);the expression of SIX4 was higher than that of TNM stageⅠ-Ⅱ,mediumly and highly differentiated pa-tients without liver invasion,common bile duct invasion,and lymph node metastasis(P<0.05).The expression of miR-103a-3p was negatively correlated with the expression of SIX4 in gallbladder cancer patients(r=-0.532,P<0.05).Fifty-nine patients died during the follow-up period.The 3-year overall survival rate of gallbladder cancer patients with low miR-103a-3p expression and high SIX4 expression was lower than that of patients with high miR-103a-3p expression and low SIX4 expression(Log-Rankχ2=6.761,5.853,both P<0.05).Liver invasion,lymph node metastasis,and high expres-sion of SIX4 were risk factors for prognosis in patients with gallbladder cancer(all P<0.05),and miR-103a-3p was a pro-tective factor(P<0.05).Conclusion The expression of miR-103a-3p is up-regulated and the expression of SIX4 is down-regulated in gallbladder cancer tissues,which is related to the malignant pathological parameters and low survival rate of gallbladder cancer.